Methylmercury stimulates arachidonic acid release and cytosolic phospholipase A2 expression in primary neuronal cultures

Cytosolic phospholipase A(2) (cPLA(2)) plays an important role in the stimulus-dependent hydrolysis of sn-2 ester bond from membrane phospholipids, releasing arachidonic acid (AA), which along with its metabolites is involved in a number of regulatory functions. The present study examined the effect of methylmercury (MeHg; 0, 2.5, 5.0 muM) on cPLA(2) activation in primary hippocampal neurons by assessing the release of 3 H-AA. A significant increase in AA release was observed in cultures treated with 5 muM MeHg (10, 30, 60 and 120 min). This effect was due to neuronal cPLA(2) activation, since it was completely abolished by arachidonyl trifluoromethyl ketone (AACOCF(3)), a specific inhibitor of cPLA(2). Additional studies confirmed, by means of western blot analysis, that MeHg (5.0 and 10 muM; 16 h) potently increases neuronal cPLA(2) protein expression. These results suggest that cPLA(2)-stimulated hydrolysis and release of AA are potential mediators of MeHg-induced neurotoxicity. (C) 2003 Elsevier Inc. All rights reserved.